Title : Identification and engineering of the cytochalasin gene cluster from Aspergillus clavatus NRRL 1 - Qiao_2011_Metab.Eng_13_723 |
Author(s) : Qiao K , Chooi YH , Tang Y |
Ref : Metab Eng , 13 :723 , 2011 |
Abstract :
Cytochalasins are a group of fungal secondary metabolites with diverse structures and bioactivities, including cytochalasin E produced by Aspergillus clavatus, which is a potent anti-angiogenic agent. Here, we report the identification and characterization of the cytochalasin gene cluster from A. clavatus NRRL 1. As a producer of cytochalasin E and K, the genome of A. clavatus was analyzed and the -30 kb ccs gene cluster was identified based on the presence of a polyketide synthase-nonribosomal peptide synthetases (PKS-NRPS) and a putative Baeyer-Villiger monooxygenase (BVMO). Deletion of the central PKS-NRPS gene, ccsA, abolished the production of cytochalasin E and K, confirming the association between the natural products and the gene cluster. Based on bioinformatic analysis, a putative biosynthetic pathway is proposed. Furthermore, overexpression of the pathway specific regulator ccsR elevated the titer of cytochalasin E from 25mg/L to 175 mg/L. Our results not only shed light on the biosynthesis of cytochalasins, but also provided genetic tools for increasing and engineering the production. |
PubMedSearch : Qiao_2011_Metab.Eng_13_723 |
PubMedID: 21983160 |
Gene_locus related to this paper: aspcl-CCSE |
Gene_locus | aspcl-CCSE |
Qiao K, Chooi YH, Tang Y (2011)
Identification and engineering of the cytochalasin gene cluster from Aspergillus clavatus NRRL 1
Metab Eng
13 :723
Qiao K, Chooi YH, Tang Y (2011)
Metab Eng
13 :723